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Regulation of miRNAs located within the imprinted DLK1-DIO3 locus at 14q32 in pituitary adenomas

Research Project

Project/Area Number 15K09435
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Endocrinology
Research InstitutionThe University of Tokushima

Principal Investigator

YOSHIMOTO Katsuhiko  徳島大学, 大学院医歯薬学研究部(歯学系), 教授 (90201863)

Co-Investigator(Kenkyū-buntansha) 岩田 武男  徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (10350399)
水澤 典子  徳島大学, 大学院医歯薬学研究部(歯学系), 助教 (80254746)
Project Period (FY) 2015-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2016: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2015: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Keywords下垂体 / 腫瘍 / インプリンティング / DNAメチル化 / 下垂体腺腫 / microRNA / メチル化 / miRNA
Outline of Final Research Achievements

Among miRNAs up-regulated in GH-producing adenomas in miRNA microarray analysis, 14q32 miRNAs were included. In contrast, these miRNAs were down-regulated in FSH/LH- and ACTH-producing adenomas, and null-cell adenomas. The adenoma type-dependent expression pattern was confirmed with qRT-PCR analysis. Although DNA copy-number changes at the 14q32 locus were not detected in all adenomas examined, abnormal methylation of CpG sites in imprinted genes within the DLK1-DIO3 locus was observed in 2 GH-producing adenomas by methylation-specific MLPA. According to DNA methylation analysis by pyrosequencing and bisulfite sequencing, methylation levels were different at each individual CpG site in intergenic DMR and MEG3-DMR, which regulate maternal gene expression at the DLK1-DIO3 locus, in 2 GH-producing adenomas. In conclusion, 14q32 miRNAs were up-regulated in sporadic GH-producing adenomas and methylation abnormalities were observed in certain GH-producing adenomas.

Report

(4 results)
  • 2017 Annual Research Report   Final Research Report ( PDF )
  • 2016 Research-status Report
  • 2015 Research-status Report
  • Research Products

    (8 results)

All 2018 2017 2016 2015

All Journal Article (1 results) (of which Peer Reviewed: 1 results,  Open Access: 1 results) Presentation (7 results) (of which Invited: 1 results)

  • [Journal Article] Growth hormone-producing pituitary adenomas in childhood and young adulthood: clinical features and outcomes.2018

    • Author(s)
      Nagata Y,Inoshita N,Fukuhara N,Yamaguchi-Okada M,Nishioka H,Iwata T,Yoshimoto K,Yamada S
    • Journal Title

      Pituitary

      Volume: 21 Issue: 1 Pages: 1-9

    • DOI

      10.1007/s11102-017-0836-4

    • NAID

      120006503287

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] 非機能性腺腫および ACTH 腺腫における 14q32 領域遺伝子の発現低下2017

    • Author(s)
      小野 信二、岩田武男、水澤典子、山田正三、吉本勝彦
    • Organizer
      第27回間脳下垂体腫瘍学会
    • Place of Presentation
      日経ホール&カンファレンスルーム(東京都千代田区)
    • Year and Date
      2017-02-24
    • Related Report
      2016 Research-status Report
  • [Presentation] 家族性下垂体腺腫の病因2016

    • Author(s)
      吉本勝彦
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      国立京都国際会館 (京都府・京都市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 内分泌異常と線維性骨異形成症の合併から、McCune-Albright症候群と診断した一例2016

    • Author(s)
      加藤 朋子、波床朋信、村上隆亮、米光新、武呂誠司、藤澤一朗、岩田武男、吉本勝彦、井下 尚子、山田尚三、隠岐尚吾
    • Organizer
      第89回日本内分泌学会学術総会
    • Place of Presentation
      国立京都国際会館 (京都府・京都市)
    • Year and Date
      2016-04-21
    • Related Report
      2016 Research-status Report
  • [Presentation] 下垂体腺腫の分子病理学2016

    • Author(s)
      吉本勝彦
    • Organizer
      第61回成長ホルモン研究会
    • Place of Presentation
      ホテルキャッスルプラザ(愛知県名古屋市中村区)
    • Year and Date
      2016-02-27
    • Related Report
      2015 Research-status Report
    • Invited
  • [Presentation] 下垂体腫瘍発生と原因遺伝子2015

    • Author(s)
      吉本勝彦
    • Organizer
      第25回 臨床内分泌代謝Update
    • Place of Presentation
      東京国際フォーラム(東京都千代田区)
    • Year and Date
      2015-11-27
    • Related Report
      2015 Research-status Report
  • [Presentation] シンポジウム「MEN1の基礎と臨床」:腫瘍発生分子機構のoverview2015

    • Author(s)
      吉本勝彦
    • Organizer
      第88回日本内分泌学会学術総会
    • Place of Presentation
      ホテルニューオオタニ東京(東京都千代田区)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report
  • [Presentation] シンポジウム「下垂体腺腫の診断と治療Update 2015」:下垂体腺腫の腫瘍化機構2015

    • Author(s)
      吉本勝彦
    • Organizer
      第88回日本内分泌学会学術総会
    • Place of Presentation
      ホテルニューオオタニ東京(東京都千代田区)
    • Year and Date
      2015-04-23
    • Related Report
      2015 Research-status Report

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Published: 2015-04-16   Modified: 2019-03-29  

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